UCSF

Bioelectric signaling is evolutionarily conserved and maintained in all living cells through the selective expression of ion channels. In excitable cells like neurons, ion channels play an essential and well characterized role in defining the properties of action potentials. Less is known about their role in non-excitable cells such as neural stem cells and neural progenitor cells. Recent studies in mice have found that the loss of a voltage-gated potassium channel, Kv1.1, leads to a dramatic increase in hippocampal neurons. The hippocampus is critical for learning and memory, and it harbors one of two well-established neurogenic niches in the adult mouse brain. Here, we investigated the role of Kv1.1 in early postnatal and adult hippocampal neurogenesis. In Chapter 2, we first examined the role of Kv1.1 in early postnatal neurogenesis. We found that loss of Kv1.1 depolarizes the membrane potential of neural progenitor cells and increases the proliferation of neural progenitor cells through the TrkB signaling pathway. Next, we assessed the role of Kv1.1 in adult hippocampal neurogenesis in Chapter 3. We observed that conditional deletion of Kv1.1 in adult neural stem cells causes an initial increase in proliferation that eventually depletes the neural stem cell pool. Furthermore, neurons produced from adult neural stem cells lacking Kv1.1 had impaired maturation and positioning. These mice also displayed hippocampal-dependent learning and memory deficits. Together, these findings support an important role for this voltage-gated ion channel in adult neurogenesis. As aberrant neurogenesis has been implicated in cognitive decline associated with aging and neurological diseases, understanding the role of Kv1.1 in adult neurogenesis provides a framework for identifying new therapeutic targets to promote healthy neurogenesis and cognition.